Mitochondrial inhibitors show preferential cytotoxicity to human pancreatic cancer PANC-1 cells under glucose-deprived conditions

Biochem Biophys Res Commun. 2010 Feb 12;392(3):460-6. doi: 10.1016/j.bbrc.2010.01.050. Epub 2010 Jan 18.


Large areas of tumor are nutrient-starved and hypoxic due to a disorganized vascular system. Therefore, we screened small molecules to identify cytotoxic agents that function preferentially in nutrient-starved conditions. We found that efrapeptin F had preferential cytotoxicity to nutrient-deprived cells compared with nutrient-sufficient cells. Because efrapeptin F acts as a mitochondrial complex V inhibitor, we examined whether inhibitors of complex I, II, III, and V function as cytotoxic agents preferentially in nutrient-deprived cells. Interestingly, these inhibitors showed preferential cytotoxicity to nutrient-deprived cells and caused cell death under glucose-limiting conditions, irrespective of the presence or absence of amino acids and/or serum. In addition, these inhibitors were preferentially cytotoxic to nutrient-deprived cells even under hypoxic conditions. Further, efrapeptin F showed antitumor activity in vivo. These data indicate that mitochondrial inhibitors show preferential cytotoxicity to cancer cells under glucose-limiting conditions, and these inhibitors offer a promising strategy for anticancer therapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology*
  • Glucose / deficiency*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors*
  • Pancreatic Neoplasms / enzymology*
  • Peptides / chemistry
  • Peptides / pharmacology*


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • complex V (mitochondrial oxidative phosphorylation system)
  • efrapeptin F
  • Mitochondrial Proton-Translocating ATPases
  • Glucose